Optical shaping system and associated apparatus and method

The optical plastic surgery system performs two-directional plasticization of the light spot, which solves the problem of low light energy utilization in the gene sequencer, achieves more uniform lighting and higher light source utilization, and improves the quality of sequencing data.

WO2025137955A1PCT designated stage expired Publication Date: 2025-07-03MGI TECH CO LTD
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Patent Information

Application Number
PCT/CN2023/142480
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-12-27
Publication Date
2025-07-03

AI Technical Summary

Technical Problem

The light sources of existing gene sequencers have problems with low light energy utilization, resulting in uneven illumination and reduced fluorescence brightness, affecting the quality of sequencing data.

Method used

An optical shaping system is adopted, including a first shaping module and a second shaping module. The light spot is shaped in two directions through a lens combination to form a rectangular light spot, and a spectroscopic prism is used to separate light of different wavelengths to avoid spot vignetting and repeated irradiation.

Benefits of technology

The utilization rate of light sources is improved, the uniformity of illumination and power density are ensured, the fluorescence brightness is reduced, and the quality of sequencing data is improved.

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Abstract

An optical shaping system, an illumination spot shaping method, a sequencer optical system, a sequencing method, and a biological sample optical test method. The optical shaping system comprises: a light source; a first shaping module comprising a plurality of lenses, wherein at least two lenses of the plurality of lenses have the same focal length, the at least two lenses having the same focal length are located between the light source and a field stop (40), and the first shaping module is configured for shaping spots emitted by the light source in a first direction; a second shaping module comprising a plurality of lenses, wherein the plurality of lenses vary in focal length, and the second shaping module is configured for shaping spots emitted by the light source in a second direction; and an objective lens (50), wherein the objective lens (50) is configured for receiving spots which are emitted by the light source and pass through the first shaping module and the second shaping module. The optical shaping system can increase the utilization of light energy.
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Description

Optical shaping system and related equipment and methods Technical Field

[0001] The present application relates to the technical field of gene detection equipment, and more specifically, to an optical shaping system, an illumination spot shaping method, a sequencer optical system, a sequencing method, and a biological sample optical detection method. Background Art

[0002] The basic principle of a gene sequencer is to use lasers to excite biological samples to produce fluorescence. This fluorescence is captured by an imaging system and then analyzed by algorithms to determine the base sequence. Traditional gene sequencers use an area array imaging system, which is slow and produces low data throughput.

[0003] To achieve higher speed, higher throughput, and lower cost in gene sequencing, the next-generation gene sequencers utilize imaging systems with a transducer-based (TDI) camera mode. Compared to area array imaging, TDI (or linear) imaging requires a thinner and longer light spot, placing higher demands on the shaping of the light spot. Currently, circular spot illumination in gene sequencer imaging systems can lead to uneven illumination, difficulty controlling the light source size, and reduced fluorescence brightness due to repeated illumination, making it unsuitable for TDI imaging.

[0004] Figure 1 shows the imaging system of an existing gene sequencer, which uses a circular light spot for illumination. Each square in Figure 1 represents an effective field of view 10, and the circle represents the illumination spot. The solid circle represents the ideal illumination spot size. A circular light spot can cause overlapping illumination of adjacent fields outside the square effective field of view 10. A small dashed circle represents a smaller light spot, resulting in uneven brightness in the effective field of view 10. A large dashed circle represents a larger light spot, increasing the overlapping illumination area of ​​adjacent fields of view.

[0005] Figure 2 shows an image captured by the area array optical system of an existing gene sequencer, showing dark corners due to a small illumination spot. Figure 3 shows the grayscale value distribution diagram along the diagonal of Figure 2. As can be seen from the figure, the existing illumination mode easily leads to uneven brightness of the illumination spot at the effective field of view 10, and some data is lost in the corners of the image due to insufficient brightness. Figure 4 shows an image captured by the area array optical system of an existing gene sequencer, showing a region with reduced brightness due to repeated illumination. Figure 5 shows the grayscale value distribution diagram in the horizontal direction of Figure 4. As can be seen from the figure, this illumination mode easily leads to repeated illumination of adjacent areas of the field of view with excitation light, resulting in reduced fluorescence brightness in these areas, affecting the image quality and thus the sequencing data quality.

[0006] Therefore, the current TDI photography mode has high requirements for the spot size, and it is difficult to find a method that can achieve uniform lighting without excessive repeated illumination. At the same time, the light source utilization rate of this lighting mode is very low, only 63.7%.

[0007] That is to say, the light source in the prior art has the problem of low light energy utilization rate.

[0008] Application Contents

[0009] The main purpose of this application is to provide an optical shaping system, an illumination spot shaping method, a sequencer optical system, a sequencing method, and a biological sample optical detection method to solve the problem of low light energy utilization in the light source in the prior art.

[0010] To achieve the above-mentioned objectives, according to one aspect of the present application, an optical shaping system is provided, comprising: a light source; a first shaping module, the first shaping module comprising a plurality of lenses, at least two of the plurality of lenses having the same focal length, and the at least two lenses having the same focal length being located between the light source and the field stop, the first shaping module being configured to shape a light spot emitted by the light source in a first direction; a second shaping module, the second shaping module comprising a plurality of lenses, the plurality of lenses having different focal lengths, the second shaping module being configured to shape a light spot emitted by the light source in a second direction; and an objective lens, the objective lens being configured to receive the light spot emitted by the light source and passing through the first shaping module and the second shaping module.

[0011] In one embodiment, the light source includes light of multiple wavelengths to form a rectangular light spot, the first direction is the short side direction of the rectangular light spot, and the second direction is the long side direction of the rectangular light spot.

[0012] In one embodiment, at least part of the lenses of the first shaping module are located between two adjacent lenses of the second shaping module, and one lens of the first shaping module and one lens of the second shaping module are included between the field stop and the objective lens.

[0013] In one embodiment, the lens in the first shaping module and the lens in the second shaping module are both cylindrical lenses, and the extension direction of the cylindrical surface of the lens in the first shaping module is perpendicular to the extension direction of the cylindrical surface of the lens in the second shaping module.

[0014] In one embodiment, the first shaping module includes three lenses, the second shaping module includes two lenses, and the three lenses of the first shaping module are located between the two lenses of the second shaping module.

[0015] In one embodiment, the first shaping module includes a first double-cemented lens and a second double-cemented lens sequentially arranged between the light source and the field stop, the first double-cemented lens and the second double-cemented lens have the same focal length, and the first double-cemented lens and the second double-cemented lens are used to achieve equal-size imaging of the light spot in the first direction and focus on the field stop.

[0016] In one embodiment, the first shaping module also includes a third double-cemented lens located between the field aperture and the objective lens. The focal length of the third double-cemented lens is different from the focal length of the first double-cemented lens. The light spot is reduced in the first direction after passing through the third double-cemented lens and the objective lens.

[0017] In one embodiment, the first double-cemented lens is formed by cementing a meniscus lens with positive optical focal length and a biconvex lens with negative optical focal length in a direction away from the light source, the second double-cemented lens is formed by cementing a biconvex lens with negative optical focal length and a meniscus lens with positive optical focal length in a direction away from the light source, and the third double-cemented lens is formed by cementing a meniscus lens with positive optical focal length and a biconvex lens with negative optical focal length in a direction away from the light source.

[0018] In one embodiment, the focal length f3 of the third doublet lens is greater than the focal length f5 of the objective lens.

[0019] In one embodiment, the distance between the first doublet lens and the second doublet lens is greater than 120 mm.

[0020] In one embodiment, the second shaping module includes a first aspheric lens, which is used to magnify the light spot emitted by the light source in the second direction and focus it at the field stop.

[0021] In one embodiment, the second shaping module also includes a fourth double-cemented lens, the first aspheric lens is located between the light source and the field stop, and the fourth double-cemented lens is located between the field stop and the objective lens. The light spot is reduced in the second direction after passing through the fourth double-cemented lens and the objective lens.

[0022] In one embodiment, the focal length f1 of the first aspheric lens is greater than 5 mm.

[0023] In one embodiment, the first aspheric lens is a plano-convex lens with positive power, and / or the fourth doublet lens is formed by cementing a meniscus lens with positive power and a double convex lens with negative power in a direction away from the light source.

[0024] In one embodiment, the optical shaping system further includes a beam splitter prism, which is located between at least two lenses with the same focal length. The beam splitter prism is used to separate light of different wavelengths emitted by the light source in a first direction.

[0025] In one embodiment, the tilt angle of the beam splitting surface of the beam splitting prism is greater than or equal to 30°.

[0026] In one embodiment, the optical shaping system further includes one or more reflectors, which are used to deflect the light path.

[0027] In one embodiment, the size of the field stop is adjustable.

[0028] According to another aspect of the present application, a method for shaping an illumination spot is provided, the shaping method comprising: starting a light source so that the light source emits a rectangular light spot; using a first shaping module to shape the light spot emitted by the light source in a first direction, the first shaping module comprising a plurality of lenses, at least two of the plurality of lenses having the same focal length, and the at least two lenses having the same focal length being located between the light source and a field stop; and using a second shaping module to shape the light spot emitted by the light source in a second direction, the second shaping module comprising a plurality of lenses, the plurality of lenses having different focal lengths.

[0029] In one embodiment, the shaping of the rectangular light spot in the length direction is achieved by adjusting the distance between two lenses with the same focal length in the first shaping module and the distance from the light source to the first lens of the second shaping module.

[0030] In one embodiment, the rectangular light spot can be enlarged or reduced in proportion by replacing objective lenses with different focal lengths.

[0031] In one embodiment, the shaping method further includes arranging a beam splitter prism between two lenses with the same focal length in the first shaping module, and adjusting the angle of the beam splitter prism to adjust the separation distance of light of different wavelengths emitted by the beam splitter prism.

[0032] In one embodiment, the first shaping module and the second shaping module shape the rectangular light spot synchronously.

[0033] According to another aspect of the present application, a sequencer optical system is provided, including a light source module, the light source module including: a laser; a multimode optical fiber coupled to the laser; a first shaping module, the first shaping module including a plurality of lenses, at least two of the plurality of lenses having the same focal length, and the at least two lenses having the same focal length being located between the optical fiber and the field stop, the first shaping module being used to shape the light spot emitted from the optical fiber in a first direction; a second shaping module, the second shaping module including a plurality of lenses, the plurality of lenses having different focal lengths, the second shaping module being used to shape the light spot emitted from the optical fiber in a second direction; and an objective lens, the objective lens being used to receive the light spot emitted by the laser and passing through the first shaping module and the second shaping module and transmit the light spot to a sample to be detected.

[0034] In one embodiment, the first shaping module includes three lenses, the second shaping module includes two lenses, and the three lenses of the first shaping module are located between the two lenses of the second shaping module.

[0035] In one embodiment, the first shaping module includes a first doublet lens, a second doublet lens, and a third doublet lens, the first doublet lens and the second doublet lens are located between the optical fiber and the field stop, and the third doublet lens is located between the field stop and the objective lens.

[0036] In one embodiment, the distance between the first doublet lens and the second doublet lens is greater than 120 mm; and / or the focal length f3 of the third doublet lens is greater than the focal length f5 of the objective lens.

[0037] In one embodiment, the second shaping module includes a first aspheric lens and a fourth doublet lens, the first aspheric lens is located between the laser and the field stop, the fourth doublet lens is located between the field stop and the objective lens, the first aspheric lens is used to magnify the light spot emitted by the laser in the second direction and focus it at the field stop, and the light spot is reduced in the second direction after passing through the fourth doublet lens and the objective lens.

[0038] In one embodiment, the focal length f1 of the first aspheric lens is greater than 5 mm.

[0039] In one embodiment, the sequencer optical system further includes a spectroscopic element, which is located between at least two lenses with the same focal length, and is configured to separate light of different wavelengths emitted by the light source in a first direction.

[0040] According to another aspect of the present application, a sequencing method is provided, comprising: outputting a rectangular light spot through a laser; compressing the rectangular light spot in the short-axis direction of the rectangular light spot through a first shaping module, the first shaping module comprising a plurality of lenses, at least two of the plurality of lenses having the same focal length, and the at least two lenses having the same focal length being located between the laser and a field stop; expanding the rectangular light spot in the long-axis direction of the rectangular light spot through a second shaping module, the second shaping module comprising a plurality of lenses, the plurality of lenses having different focal lengths; separating the rectangular light spot in the short-axis direction using a spectroscopic element; and transmitting the shaped and spectroscopically split rectangular light spot through an objective lens to a sample to be detected.

[0041] In one embodiment, the step of outputting a rectangular light spot through a laser includes: providing a laser beam to a multimode optical fiber through a laser; guiding the laser beam through the multimode optical fiber, and shaping the light beam output from the output end of the multimode optical fiber into a rectangular light spot by a collimator.

[0042] In one embodiment, the step of compressing the rectangular light spot in the short axis direction of the rectangular light spot by the first shaping module and the step of expanding the rectangular light spot in the long axis direction of the rectangular light spot by the second shaping module are performed simultaneously.

[0043] According to another aspect of the present application, a method for optical detection of biological samples is provided, comprising: outputting a rectangular light spot through a laser; expanding the rectangular light spot in the long axis direction of the rectangular light spot through a first shaping module, the first shaping module comprising a plurality of lenses, at least two of the plurality of lenses having the same focal length, and the at least two lenses having the same focal length being located between the laser and a field stop; compressing the rectangular light spot in the short axis direction of the rectangular light spot through a second shaping module, the second shaping module comprising a plurality of lenses, the plurality of lenses having different focal lengths; and transmitting the shaped rectangular light spot through an objective lens to a sample to be detected.

[0044] In one embodiment, the sample to be tested is a tissue sample or a nucleic acid sequencing library.

[0045] Applying the technical solution of the present application, an optical shaping system includes a light source, a first shaping module, a second shaping module and an objective lens. The first shaping module includes multiple lenses, at least two of the multiple lenses have the same focal length, and the at least two lenses with the same focal length are located between the light source and the field stop. The first shaping module is used to shape the light spot emitted by the light source in a first direction; the second shaping module includes multiple lenses, the multiple lenses have different focal lengths, and the second shaping module is used to shape the light spot emitted by the light source in a second direction; the objective lens is used to receive the light spot emitted by the light source and passed through the first shaping module and the second shaping module.

[0046] The present application shapes the light spot in two directions by providing a first shaping module and a second shaping module to form the desired light spot shape. By providing the first shaping module and the second shaping module to separately control the divergence angle of the light spot in two directions, vignetting of the light spot is avoided. The system can also decouple the mutual interference of the two perpendicular directions during the shaping process, and the structure is easy to adjust. The optical shaping system of the present application shapes the light spot, thereby overcoming the problem of uneven light spot illumination, greatly improving the uniformity and power density of the illumination, and avoiding problems such as reduced fluorescence brightness caused by repeated irradiation, thereby greatly improving the utilization rate of the light source. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] The drawings constituting part of this specification are intended to provide a further understanding of the present application. The illustrative embodiments of the present application and their descriptions are intended to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0048] FIG1 is a schematic diagram showing an illumination spot on a field of view in an area array mode in the prior art;

[0049] FIG2 shows a picture taken by the area array optical system when the light spot in FIG1 is smaller;

[0050] FIG3 shows a grayscale value distribution curve on the diagonal line of the image in FIG2 ;

[0051] FIG4 shows a picture taken by the area array optical system when the light spot in FIG1 is relatively large;

[0052] FIG5 shows a grayscale value distribution curve in the horizontal direction of the image in FIG4 ;

[0053] FIG6 shows a light path diagram of the optical shaping system of the present application in the short side direction and the long side direction;

[0054] FIG7 shows a light path diagram of the optical shaping system of the present application when it has a beam splitter prism;

[0055] FIG8 is a schematic diagram showing an angle of the beam splitter prism in FIG7 ;

[0056] FIG9 shows a schematic diagram of the optical path of the optical shaping system in FIG7 ;

[0057] FIG10 shows a simulation result diagram of an optical shaping system according to an embodiment of the present application;

[0058] FIG11 shows a simulation result diagram of an optical shaping system according to another embodiment of the present application;

[0059] FIG12 shows a photograph of the light spot output by the optical shaping system of the present application in the linear array optical system of a gene sequencer;

[0060] FIG. 13 shows a grayscale value distribution diagram in the horizontal direction of the picture in FIG. 12 .

[0061] Among them, the above-mentioned drawings include the following figure marks: 10, effective field of view; 21, first doublet lens; 22, second doublet lens; 23, third doublet lens; 31, first aspheric lens; 32, fourth doublet lens; 40, field stop; 50, objective lens; 60, dichroic prism; 61, dichroic surface. DETAILED DESCRIPTION

[0062] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments can be combined with each other. The present application will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0063] It should be noted that, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0064] In this application, unless otherwise specified, directional words such as "up, down, top, bottom" are usually used with reference to the directions shown in the drawings, or with reference to the components themselves in the vertical, perpendicular or gravity direction; similarly, for ease of understanding and description, "inside and outside" refer to the inside and outside relative to the outline of each component itself, but the above directional words are not used to limit this application.

[0065] In order to solve the problem of low light energy utilization rate of light sources in the prior art, the present application provides an optical shaping system, an illumination spot shaping method, a sequencer optical system, a sequencing method, and a biological sample optical detection method.

[0066] As shown in Figures 6 to 13, the optical shaping system includes a light source, a first shaping module, a second shaping module and an objective lens 50. The first shaping module includes multiple lenses, at least two of the multiple lenses have the same focal length, and the at least two lenses with the same focal length are located between the light source and the field stop 40. The first shaping module is used to shape the light spot emitted by the light source in a first direction; the second shaping module includes multiple lenses, the multiple lenses have different focal lengths, and the second shaping module is used to shape the light spot emitted by the light source in a second direction; the objective lens 50 is used to receive the light spot emitted by the light source through the first shaping module and the second shaping module.

[0067] The present application shapes the light spot in two directions by providing a first shaping module and a second shaping module to form the desired light spot shape. By providing the first shaping module and the second shaping module to separately control the divergence angle of the light spot in two directions, vignetting of the light spot is avoided. The system can also decouple the mutual interference of the two perpendicular directions during the shaping process, and the structure is easy to adjust. The optical shaping system of the present application shapes the light spot, thereby overcoming the problem of uneven light spot illumination, greatly improving the uniformity and power density of the illumination, and avoiding problems such as reduced fluorescence brightness caused by repeated irradiation, thereby greatly improving the utilization rate of the light source.

[0068] Specifically, the light source includes light of multiple wavelengths to form a rectangular light spot, with the first direction being the short side of the rectangular light spot, and the second direction being the long side of the rectangular light spot. Specifically, the first shaping module is used to shape the rectangular light spot in the short side direction, and the second shaping module is used to shape the rectangular light spot in the long side direction.

[0069] As shown in FIG6 , at least some of the lenses of the first shaping module are located between two adjacent lenses of the second shaping module. One lens of the first shaping module and one lens of the second shaping module are located between the field stop 40 and the objective lens 50. Both the lenses of the first shaping module and the lenses of the second shaping module are cylindrical lenses. The cylindrical surfaces of the lenses of the first shaping module extend perpendicularly to the cylindrical surfaces of the lenses of the second shaping module. Furthermore, the cylindrical surfaces of the lenses of the first shaping module extend along a first direction, while the cylindrical surfaces of the lenses of the second shaping module extend along a second direction, with the first direction being perpendicular to the second direction.

[0070] As shown in Figure 6, the first shaping module includes three lenses: a first doublet lens 21, a second doublet lens 22, and a third doublet lens 23. The first doublet lens 21 and the second doublet lens 22 are positioned away from the light source between the light source and the field stop 40. The first doublet lens 21 and the second doublet lens 22 have the same focal length. The first doublet lens 21 and the second doublet lens 22 are used to achieve equal imaging of the rectangular light spot in the first direction and focus it on the field stop 40. The field stop 40 is located in the first shaping module. The third doublet lens 23 is positioned between the field stop 40 and the objective lens 50. The focal length of the third doublet lens 23 is different from that of the first doublet lens 21. After passing through the third doublet lens 23 and the objective lens 50, the light spot is reduced in the first direction.

[0071] As shown in Figure 6 , the second shaping module includes two lenses: a first aspheric lens 31 and a fourth doublet lens 32. The first aspheric lens 31 is located between the light source and the field stop 40, while the fourth doublet lens 32 is located between the field stop 40 and the objective lens 50. Specifically, the first aspheric lens 31 is located between the light source and the first doublet lens 21, while the fourth doublet lens 32 is located between the third doublet lens 23 and the objective lens 50. The first aspheric lens 31 is used to amplify the light spot emitted by the light source in the second direction and focus it on the field stop 40. The light spot is then reduced in the second direction after passing through the fourth doublet lens 32 and the objective lens 50. As can be seen from the figure, the three lenses of the first shaping module are located between the two lenses of the second shaping module.

[0072] As shown in Figure 6, the optical shaping system of the present application can shape the rectangular light spot emitted by the light source into a linear light spot. In Figure 6, the upper part is a cross-sectional view of the optical shaping system in the short direction, and the lower part is a cross-sectional view of the optical shaping system in the long direction.

[0073] In the short-side direction, the rectangular light spot emitted by the light source passes through two first and second doublet lenses 21 and 22 with the same focal length of f2, achieving a 1:1 shaping at the field stop 40. In the long-side direction, the rectangular light spot emitted by the light source passes through the first aspheric lens 31 with a focal length of f1, magnified in the long-side direction, and focused at the field stop 40. Assuming the aspect ratio of the rectangular light spot is x:y, and the magnification of the first aspheric lens 31 is β2, then at the field stop 40, the length and width of the rectangular light spot are: x' = β2 * x; y' = y;

[0074] The magnification β2 is related to the distance between the light source's exit surface and the first aspheric lens 31, the first doublet lens 21, and the second doublet lens 22. In the short-side direction, after reaching the field stop 40, the light passes through the third doublet lens 23 with a focal length of f3, which shapes it into parallel light along the short side. The light then passes through the objective lens 50 with a focal length of f5, reducing the short-side direction of the light spot by a certain percentage. The lateral magnification of the light spot in the short-side direction after passing through the third doublet lens 23 and the objective lens 50 is: β3 = f5 / f3;

[0075] In the longitudinal direction, the light reaches the field stop 40 and passes through the fourth doublet lens 32 with a focal length of f4, which then parallelizes the longitudinal direction of the light spot. The light then passes through the objective lens 50 with a focal length of f5, reducing the longitudinal direction of the light spot by a certain percentage. The lateral magnification of the light spot in the longitudinal direction after passing through the fourth doublet lens 32 and the objective lens 50 is: β4 = f5 / f4;

[0076] The length and width of the rectangular spot after shaping are: X = β4*x'; Y = β3*y';

[0077] That is, the relationship between the original rectangular spot emitted from the light source and the target spot size is: X = β2*(f5 / f4)*x; Y = (f5 / f3)*y;

[0078] As shown in FIG6 , the light between the first doublet lens 21 and the second doublet lens 22 is parallel light in the short side direction, creating a freely adjustable space for shaping in the long side direction; adjusting the distance from the first aspheric lens 31 to the light source and the distance between the first doublet lens 21 and the second doublet lens 22 can change the magnification β2, that is, change the spot length at the position of the field stop 40, thereby achieving the adjustment of the illumination spot length.

[0079] In addition, the size of the field of view diaphragm 40 of the present application can be adjusted, and the length of the light spot can be further adjusted by blocking the length of the field of view diaphragm 40. The accuracy requirements of the position of the field of view diaphragm 40 for the adjustable field of view diaphragm 40 are greatly reduced compared to the accuracy requirements for directly adjusting the field of view on the end face of the light source.

[0080] In addition, in the shaping light path of the present application, both in the long side direction and the short side direction, a double-cemented cylindrical lens made of cylindrical lenses of different materials is used to eliminate chromatic aberration, thereby reducing the width and length differences of the two wavelength spots.

[0081] In a specific embodiment of the present application, the focal length f1 of the first aspheric lens 31 is greater than 5 mm. The length of the rectangular light spot in the longitudinal direction decreases as the focal length f1 increases. The first aspheric lens 31 is a plano-convex lens with positive optical power.

[0082] Specifically, the distance between the light source and the aperture of the first aspheric lens 31 is in the range of f1 to 2f1 to achieve a magnification effect, and the magnification β2 is adjusted by adjusting the distance.

[0083] Specifically, the first doublet lens 21, the second doublet lens 22, and the third doublet lens 23 are all formed by bonding a positive power lens and a negative power lens. The proper combination of positive and negative power facilitates the proper arrangement of the lenses, while also facilitating the elimination of chromatic aberration and correction of distortion.

[0084] As shown in Figure 6, the first doublet lens 21 and the second doublet lens 22 are arranged relative to each other and placed in opposite directions. Specifically, the first doublet lens 21 is composed of a positive-power meniscus lens and a negative-power biconvex lens glued together in the direction away from the light source, and the second doublet lens 22 is composed of a negative-power biconvex lens and a positive-power meniscus lens glued together in the direction away from the light source. The distance between the first doublet lens 21 and the second doublet lens 22 is greater than 120 mm. The length of the light spot in the longitudinal direction increases as the distance between the first doublet lens 21 and the second doublet lens 22 increases. By constraining the distance between the first doublet lens 21 and the second doublet lens 22, it is convenient to adjust the length of the light spot. The choice of focal length of the first doublet lens 21 and the second doublet lens 22 only affects the placement of the lenses and does not affect the size of the light spot in the width direction.

[0085] Specifically, the thickness of the rectangular light spot in the width direction will decrease as the focal length f3 of the third double-cemented lens 23 increases. In order to achieve the reduction of the light spot in the width direction, it is necessary to set the focal length f3 of the third double-cemented lens 23 to be greater than the focal length f5 of the objective lens 50. At the same time, the third double-cemented lens 23 is planned to be composed of a meniscus lens with positive optical focal length and a double convex lens with negative optical focal length glued together in the direction away from the light source.

[0086] In the present application, the front-to-back positions of the first aspheric lens 31 and the first doublet lens 21 cannot be changed. When the first aspheric lens 31 is located in front of the first doublet lens 21, the focal length f2 of the first doublet lens 21 is greater than the sum of the focal length f1 of the first aspheric lens 31 and the thickness of the first aspheric lens 31. When the first doublet lens 21 is located in front of the first aspheric lens 31, the focal length f1 of the first aspheric lens 31 is greater than the sum of the focal length f2 of the first doublet lens 21 and the total thickness of the first doublet lens 21.

[0087] In the present application, the focal length f4 of the fourth doublet lens 32 is greater than the sum of the focal length f3 of the third doublet lens 23 and the total thickness of the third doublet lens 23. Since the rectangular light spot shrinks as the length f4 increases in the longitudinal direction, f4 is set greater than 1 to achieve magnification of the light spot in the x-direction. Furthermore, the fourth doublet lens 32 is designed to be formed by cementing a meniscus lens with positive optical power and a biconvex lens with negative optical power in the direction away from the light source.

[0088] In the present application, the front-to-back positions of the third doublet lens 23 and the fourth doublet lens 32 can be changed. If, as shown in FIG6 , the third doublet lens 23 is positioned before the fourth doublet lens 32, the focal lengths f3 and f4 must satisfy the following requirement: focal length f4 is greater than the sum of focal length f3 and the total thickness of the third doublet lens 23. If the fourth doublet lens 32 is positioned before the third doublet lens 23, focal length f3 is greater than the sum of focal length f4 and the total thickness of the fourth doublet lens 32. However, the positions of the lenses before and after the field stop 40 cannot be changed.

[0089] In the present application, the focal length f1 of the first aspheric lens 31, the focal length f2 of the first doublet lens 21 and the second doublet lens 22, the focal length f3 of the third doublet lens 23, the focal length f4 of the fourth doublet lens 32 and the focal length f5 of the objective lens 50 are all greater than zero.

[0090] In the present application, the spot size in front of the objective lens 50 is less than or equal to the entrance pupil size of the objective lens 50, and the length of the shaped spot is less than or equal to the field of view of the objective lens 50. After the rectangular spot emitted by the light source passes through the optical shaping system of the present application, a linear spot with a long side size greater than or equal to twice the short side size can be obtained.

[0091] The optical shaping system of the present application is described below with reference to specific embodiments. The optical shaping system of the present application can be applied to a TDI camera optical system to shape a light spot.

[0092] As shown in FIG6 , the light source is a rectangular light source with uniform intensity generated by coupling Gaussian light into a multimode rectangular optical fiber. The rectangular light spot formed by the light source has a length of x = 450 μm and a width of y = 150 μm. The optical shaping system of the present application shapes the rectangular light spot into a light spot with a length of X = 1.6 mm and a width of Y = 0.06 mm.

[0093] The specific scheme is as follows: in the short-side direction, the rectangular light spot passes through the first doublet lens 21 and the second doublet lens 22 with a focal length f2 of 25mm, and forms a width y' = 150um at the field stop 40; then passes through the third doublet lens 23 with a focal length f3 of 25mm and the objective lens 50 with a focal length f5 of 10mm, and the short side of the light spot is reduced to Y = (f5 / f3) * y' = 60um; in the long-side direction, the rectangular light spot passes through the first doublet lens 21 and the second doublet lens 22 with a focal length f2 of 25mm, and forms a width y' = 150um at the field stop 40; then passes through the third doublet lens 23 with a focal length f3 of 25mm and the objective lens 50 with a focal length f5 of 10mm, and the short side of the light spot is reduced to Y = (f5 / f3) * y' = 60um The first aspheric lens 31 with a focal length f1 of 10 mm is focused on the position of the field stop 40. The appropriate distance is adjusted to make the magnification β2 = 23.1, so that the length of the rectangular light spot at the field stop 40 is x' = β2*x = 10.4 mm. From the field stop 40, it passes through the fourth doublet lens 32 with a focal length f4 of 65 mm and the objective lens 50 with a focal length f5 of 10 mm, and the long side of the light spot is reduced to X = (f5 / f4)*x' = 1.6 mm.

[0094] The light source of the present application has two wavelengths of laser light, which can then excite different fluorescent dyes to emit fluorescence of different wavelengths. For example, four dyes are used to bind to the four bases ACGT to stimulate the emission of fluorescence of different wavelengths, and the type of base is located by identifying the different wavelengths. The two wavelengths of laser light are coupled into the same rectangular multimode optical fiber with an aspect ratio of 1:3. In order to reduce the laser power density at the same position and thus reduce damage to the biological sample, a beam splitter prism 60 can be provided in the optical shaping system, so that the beam splitter prism 60 separates the two wavelengths of light by a certain distance in the short-side direction.

[0095] In the specific embodiment shown in Figures 7 and 8, the dichroic prism 60 is located between at least two lenses with the same focal length. Specifically, the dichroic prism 60 is located in the parallel light path between the first double-cemented lens 21 and the second double-cemented lens 22. The inclination angle of the dichroic surface 61 of the dichroic prism 60 is greater than or equal to 30°. The angle of the dichroic surface 61 of the dichroic prism 60 can be expanded, for example, it can be 40°, 50°, 60°, 70°, or a larger angle. As the angle increases, the relative distance between light spots of different wavelengths increases. The inclination angle of the dichroic surface 61 can be set according to specific needs. This embodiment uses a dichroic prism 60 with a dichroic surface 61 angle of 33°, so that the two wavelengths of light are separated by 120um in the short side direction.

[0096] FIG9 shows a simulated optical path diagram of the optical shaping system using a beam splitter prism 60. The optical shaping system also includes one or more reflectors, which are used to deflect the optical path. For example, the reflector can be positioned between the third doublet lens 23 and the fourth doublet lens 32. Of course, one or more reflectors can be selected as needed and positioned at desired locations to minimize the overall size of the optical shaping system.

[0097] Figure 10 shows the simulation results of the optical shaping system in Figure 9. The simulation input is a 1W laser. When the field stop 40 width is 10.4mm, 0.964W of laser light is received at the image plane, resulting in an energy utilization rate of 96.4%. The spot length is nearly flat within 1.6mm, and the separation between the two wavelengths is 0.12mm. The spot length can be adjusted using the adjustable iris at the position of the field stop 40. For example, when the iris length is set to 9.1mm, the spot length at the image plane is 1.4mm, as shown in Figure 11.

[0098] As shown in Figures 12 and 13, the photographic results and grayscale value distribution diagrams of the optical shaping system of the present application in the linear array optical system of the gene sequencer are shown. As can be seen from the figures, the illumination uniformity of the final light spot is 97%.

[0099] In summary, the optical shaping system of the present application can reasonably adjust the length and width of the rectangular light spot to output a light spot of the required size, ensure the uniformity of illumination, and eliminate the problem of repeated irradiation; at the same time, it improves the utilization rate of the light source, up to 96%; at the same time, the optical shaping system has a high tolerance for the position accuracy of the lens, reduces the difficulty of installation and adjustment, reduces the installation time and improves production efficiency; in addition, the optical shaping system of the present application uses the first module and the second module to independently adjust the long side direction and the short side direction of the light spot, so that the length and width of the light spot are independently controllable.

[0100] The present application also provides a method for shaping an illumination spot. The shaping method is implemented, for example, using the above-mentioned optical shaping system, and includes:

[0101] Start the light source so that the light source emits a rectangular light spot;

[0102] A first shaping module is used to shape the light spot emitted by the light source in a first direction. The first shaping module includes a plurality of lenses, at least two of the plurality of lenses have the same focal length, and the at least two lenses with the same focal length are located between the light source and the field stop 40.

[0103] A second shaping module is used to shape the light spot emitted by the light source in a second direction. The second shaping module includes a plurality of lenses, and the focal lengths of the plurality of lenses are different.

[0104] Specifically, by adjusting the distance between two lenses with the same focal length in the first shaping module and the distance from the light source to the first lens of the second shaping module, the shaping of the rectangular light spot in the length direction is achieved.

[0105] In addition, the rectangular light spot can be proportionally enlarged or reduced by replacing the objective lens 50 with a different focal length. Simultaneously, the length and width of the light spot can be adjusted by changing the focal length f1 of the first aspheric lens 31, the focal length f2 of the first and second doublet lenses 21 and 22, the focal length f3 of the third doublet lens 23, and the focal length f4 of the fourth doublet lens 32.

[0106] In addition, by adjusting the angle of the beam splitter prism 60, the separation distance of the light of different wavelengths emitted by the beam splitter prism 60 can be adjusted. In the present application, the first shaping module and the second shaping module shape the rectangular light spot synchronously.

[0107] In a specific embodiment of the present application, when the length of the rectangular light spot emitted by the light source is x and the width is y, and the length of the rectangular light spot needs to be adjusted to X and the width to Y,

[0108] In the short side direction, the rectangular light spot passes through the first double-cemented lens 21 and the second double-cemented lens 22 with a focal length of f2 to form a light spot with a width of y' at the field aperture 40, and then passes through the third double-cemented lens 23 with a focal length of f3 and the objective lens 50 with a focal length of f5, and the short side of the light spot is reduced to Y = (f5 / f3) * y'. Therefore, f2, f3 and f5 can be reasonably set according to this formula.

[0109] In the long-side direction, the rectangular light spot is focused to the position of the field stop 40 through the first aspheric lens 31 with a focal length of f1. By adjusting the appropriate distance to achieve the magnification β2, the length of the rectangular light spot at the field stop 40 is x'=β2*x. From the field stop 40, the fourth doublet lens 32 with a focal length of f4 and the objective lens 50 with a focal length of f5 reduce the long side of the light spot to X=(f5 / f4)*x'. Therefore, f1, f5, and f4 can be reasonably set according to this formula.

[0110] It should be noted that the distance between the light source and the aperture of the first aspheric lens 31 is in the range of f1 to 2f1 to achieve a magnifying effect, and the magnification β2 is adjusted by adjusting the distance.

[0111] The present application also provides a sequencer optical system, including a light source, a first shaping module, a second shaping module and an objective lens 50; the light source includes a laser and a multimode optical fiber coupled to the laser; the first shaping module includes multiple lenses, at least two of the multiple lenses have the same focal length, and at least two lenses with the same focal length are located between the optical fiber and the field stop 40, and the first shaping module is used to shape the light spot emitted from the optical fiber in a first direction; the second shaping module includes multiple lenses, and the multiple lenses have different focal lengths, and the second shaping module is used to shape the light spot emitted from the optical fiber in a second direction; the objective lens 50 is used to receive the light spot emitted by the laser through the first shaping module and the second shaping module and transmit the light spot to the sample to be detected.

[0112] Inside the laser, two wavelengths of Gaussian light are coupled into the same multimode rectangular optical fiber to achieve uniform distribution of the spot energy and obtain a homogenized rectangular spot.

[0113] Specifically, the first shaping module includes three lenses, and the second shaping module includes two lenses. The three lenses of the first shaping module are located between the two lenses of the second shaping module. The first shaping module includes a first doublet lens 21, a second doublet lens 22, and a third doublet lens 23. The first and second doublet lenses 21, 22 are located between the optical fiber and the field stop 40, while the third doublet lens 23 is located between the field stop 40 and the objective lens 50. The distance between the first doublet lens 21 and the second doublet lens 22 is greater than 120 mm; the focal length f3 of the third doublet lens 23 is greater than the focal length f5 of the objective lens 50.

[0114] Specifically, the second shaping module includes a first aspheric lens 31 and a fourth doublet lens 32. The first aspheric lens 31 is positioned between the light source and the field stop 40, while the fourth doublet lens 32 is positioned between the field stop 40 and the objective lens 50. The first aspheric lens 31 is used to amplify the light spot emitted by the light source in the second direction and focus it at the field stop 40. The light spot is then reduced in the second direction after passing through the fourth doublet lens 32 and the objective lens 50. The focal length f1 of the first aspheric lens 31 is greater than 5 mm.

[0115] Optionally, the sequencer optical system further includes a spectroscopic element, which is located between at least two lenses with the same focal length, and is used to separate light of different wavelengths emitted by the light source in a first direction.

[0116] In addition, the optical path structure of the sequencer optical system, the specific focal length and shape of the lens therein, and other parameters are the same as those of the above-mentioned optical shaping system. Please refer to the above description and will not be repeated here.

[0117] The present application also provides a sequencing method, which is implemented using the above-mentioned sequencer optical system, including: outputting a rectangular light spot through a light source; compressing the rectangular light spot in the short axis direction of the rectangular light spot through a first shaping module, the first shaping module including multiple lenses, at least two of the multiple lenses having the same focal length, and the at least two lenses with the same focal length are located between the light source and the field stop 40; expanding the rectangular light spot in the long axis direction of the rectangular light spot through a second shaping module, the second shaping module including multiple lenses, the multiple lenses having different focal lengths; using a spectrometer to separate the rectangular light spot in the short axis direction; and transmitting the shaped and spectroscopic rectangular light spot through the objective lens 50 to the sample to be detected.

[0118] Specifically, the step of outputting a rectangular light spot through a light source includes: providing a laser beam to a multimode optical fiber through a laser; guiding the laser beam through the multimode optical fiber; and shaping the light beam output from the output end of the multimode optical fiber into a rectangular light spot using a collimator. The steps of compressing the rectangular light spot along its short axis by a first shaping module and expanding the rectangular light spot along its long axis by a second shaping module are performed simultaneously.

[0119] It should be noted that the specific details of the steps before using the beam splitter to separate the rectangular light spot along the short axis can be referred to the above-mentioned shaping method and will not be repeated here. In this step, the beam splitter is a beam splitter prism 60. The angle of the beam splitter surface 61 of the beam splitter prism 60 can affect the separation distance of light of different wavelengths. The angle of the beam splitter surface 61 of the beam splitter prism 60 can be greater than 30°.

[0120] The present application also provides a method for optical detection of biological samples, which includes: outputting a rectangular light spot through a light source; expanding the rectangular light spot in the long axis direction of the rectangular light spot through a first shaping module, the first shaping module including multiple lenses, at least two of the multiple lenses having the same focal length, and at least two lenses with the same focal length being located between the light source and the field stop 40; compressing the rectangular light spot in the short axis direction of the rectangular light spot through a second shaping module, the second shaping module including multiple lenses, the multiple lenses having different focal lengths; and transmitting the shaped rectangular light spot to the sample to be detected through the objective lens 50.

[0121] The present invention's method for optically detecting biological samples involves adjusting a rectangular light spot so that it expands in length and compresses in width, thereby obtaining a desired light spot size. This light spot is then applied to the field of view of the sample to be detected. The specific method for adjusting the size of the rectangular light spot can be found above and will not be further elaborated here.

[0122] Specifically, the sample to be tested is a tissue sample or a nucleic acid sequencing library.

[0123] Obviously, the embodiments described above are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of this application.

[0124] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, tasks, devices, components and / or combinations thereof.

[0125] It should be noted that the terms "first," "second," and the like in the present specification, claims, and drawings are used to distinguish similar objects, and are not necessarily used to describe a particular order or precedence. It should be understood that the terms used in this manner are interchangeable where appropriate, such that the embodiments of the present invention described herein can be implemented in an order other than that illustrated or described herein.

[0126] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application. Various modifications and variations are possible for those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. An optical shaping system, characterized in that, Comprising: A light source; A first shaping module, the first shaping module includes a plurality of lenses, at least two of the plurality of lenses have the same focal length, and at least two lenses with the same focal length are located between the light source and the field stop (40), the first shaping module is used to shape the light spot emitted by the light source in a first direction; A second shaping module, the second shaping module includes a plurality of lenses, the focal lengths of the plurality of lenses are different, the second shaping module is used to shape the light spot emitted by the light source in a second direction; An objective lens (50), the objective lens (50) is used to receive the light spot emitted by the light source that has passed through the first shaping module and the second shaping module.

2. The optical shaping system according to claim 1, wherein The light source includes lights of multiple wavelengths to form a rectangular light spot, the first direction is the short side direction of the rectangular light spot, and the second direction is the long side direction of the rectangular light spot.

3. The optical shaping system according to claim 1, wherein At least part of the lenses of the first shaping module are located between two adjacent lenses of the second shaping module, and between the field stop (40) and the objective lens (50) includes one lens of the first shaping module and one lens of the second shaping module.

4. The optical shaping system according to claim 1, wherein The lenses in the first shaping module and the lenses in the second shaping module are both cylindrical lenses, and the extending direction of the cylinder surface of the lenses in the first shaping module is perpendicular to the extending direction of the cylinder surface of the lenses in the second shaping module.

5. The optical shaping system according to claim 1, wherein The first shaping module includes three lenses, the second shaping module includes two lenses, and the three lenses of the first shaping module are located between the two lenses of the second shaping module.

6. The optical shaping system according to claim 1, wherein The first shaping module includes a first doublet lens (21) and a second doublet lens (22) sequentially arranged between the light source and the field stop (40), the first doublet lens (21) and the second doublet lens (22) have the same focal length, and the first doublet lens (21) and the second doublet lens (22) are used to realize equal-sized imaging of the light spot in the first direction and focus on the field stop (40).

7. The optical shaping system according to claim 6, wherein The first shaping module further includes a third doublet lens (23) located between the field stop (40) and the objective lens (50), the focal length of the third doublet lens (23) is different from the focal length of the first doublet lens (21), and the light spot is reduced in the first direction after passing through the third doublet lens (23) and the objective lens (50).

8. The optical shaping system according to claim 7, characterized in that The first doublet lens (21) is glued by a meniscus lens with positive optical power and a biconvex lens with negative optical power in the direction away from the light source, the second doublet lens (22) is glued by a biconvex lens with negative optical power and a meniscus lens with positive optical power in the direction away from the light source, and the third doublet lens (23) is glued by a meniscus lens with positive optical power and a biconvex lens with negative optical power in the direction away from the light source.

9. The optical shaping system according to claim 7, wherein The focal length f3 of the third doublet lens (23) is greater than the focal length f5 of the objective lens (50).

10. The optical shaping system according to claim 6, wherein The distance between the first doublet lens (21) and the second doublet lens (22) is greater than 120 mm.

11. The optical shaping system according to claim 1, wherein, The second shaping module includes a first aspherical lens (31), and the first aspherical lens (31) is configured to magnify the light spot emitted by the light source in the second direction and focus it at the field stop (40).

12. The optical shaping system according to claim 11, wherein, The second shaping module further includes a fourth doublet lens (32). The first aspherical lens (31) is located between the light source and the field stop (40), and the fourth doublet lens (32) is located between the field stop (40) and the objective lens (50). The light spot is reduced in the second direction after passing through the fourth doublet lens (32) and the objective lens (50).

13. The optical shaping system according to claim 11, wherein The focal length f1 of the first aspherical lens (31) is greater than 5 mm.

14. The optical shaping system according to claim 12, wherein The first aspherical lens (31) is a plano-convex lens with positive optical power, and / or the fourth doublet lens (32) is formed by gluing a meniscus lens with positive optical power and a biconvex lens with negative optical power along the direction away from the light source.

15. The optical shaping system according to any one of claims 1 to 14, characterized in that, The optical shaping system further includes a beam splitter prism (60). The beam splitter prism (60) is located between at least two lenses with the same focal length, and the beam splitter prism (60) is configured to separate lights with different wavelengths emitted by the light source in the first direction.

16. The optical shaping system according to claim 15, wherein The tilt angle of the beam splitting surface of the beam splitter prism (60) is greater than or equal to 30°.

17. The optical shaping system according to any one of claims 1 to 14, characterized in that The optical shaping system further includes a reflector, and the reflector is one or more, and the reflector is configured to deflect the optical path.

18. The optical shaping system according to any one of claims 1 to 14, characterized in that, The size of the field stop (40) is set to be adjustable.

19. A method for shaping an illumination light spot, characterized in that, The shaping method includes: Starting the light source to make the light source emit a rectangular light spot; Using a first shaping module to shape the light spot emitted by the light source in the first direction. The first shaping module includes a plurality of lenses, and at least two of the plurality of lenses have the same focal length, and at least two lenses with the same focal length are located between the light source and the field stop (40); Using a second shaping module to shape the light spot emitted by the light source in the second direction. The second shaping module includes a plurality of lenses, and the focal lengths of the plurality of lenses are different.

20. The method for shaping an illumination light spot according to claim 19, wherein By adjusting the distance between two lenses with the same focal length in the first shaping module and the distance from the light source to the first lens of the second shaping module, the shaping of the rectangular light spot in the length direction is achieved.

21. The shaping method of the illumination spot according to claim 19, characterized in that, By replacing the objective lens (50) with different focal lengths, the equal-proportion magnification or reduction of the rectangular light spot is achieved.

22. The shaping method of the illumination spot according to claim 19, characterized in that, The shaping method further includes setting a beam splitter prism (60) between two lenses with the same focal length in the first shaping module, and by adjusting the angle of the beam splitter prism (60), the adjustment of the separation distance of lights with different wavelengths emitted by the beam splitter prism (60) is achieved.

23. The method for shaping the illumination spot according to claim 19, characterized in that, The shaping of the rectangular light spot by the first shaping module and the second shaping module is performed synchronously.

24. A sequencing instrument optical system, characterized in that, Including a light source module, the light source module includes: A laser; A multimode optical fiber coupled to the laser; The first shaping module, the first shaping module includes a plurality of lenses, at least two of the plurality of lenses have the same focal length, and at least two lenses with the same focal length are located between the optical fiber and the field stop (40), and the first shaping module is used to shape the spot emitted from the optical fiber in the first direction; The second shaping module, the second shaping module includes a plurality of lenses, the focal lengths of the plurality of lenses are different, and the second shaping module is used to shape the spot emitted from the optical fiber in the second direction; The objective lens (50), the objective lens (50) is used to receive the spot that has passed through the first shaping module and the second shaping module and is emitted by the laser and transmit the spot to the sample to be detected.

25. The sequencing instrument optical system according to claim 24, characterized in that, The first shaping module includes three lenses, the second shaping module includes two lenses, and the three lenses of the first shaping module are located between the two lenses of the second shaping module.

26. The sequencing instrument optical system according to claim 24, characterized in that, The first shaping module includes a first doublet lens (21), a second doublet lens (22) and a third doublet lens (23), the first doublet lens (21) and the second doublet lens (22) are located between the optical fiber and the field stop (40), and the third doublet lens (23) is located between the field stop (40) and the objective lens (50).

27. The sequencing instrument optical system according to claim 26, wherein The distance between the first doublet lens (21) and the second doublet lens (22) is greater than 120 mm; and / or the focal length f3 of the third doublet lens (23) is greater than the focal length f5 of the objective lens (50).

28. The sequencing instrument optical system according to claim 24, wherein The second shaping module includes a first aspherical lens (31) and a fourth doublet lens (32), the first aspherical lens (31) is located between the laser and the field stop (40), the fourth doublet lens (32) is located between the field stop (40) and the objective lens (50), the first aspherical lens (31) is used to magnify the spot emitted by the laser in the second direction and focus it at the field stop (40), and the spot is reduced in the second direction after passing through the fourth doublet lens (32) and the objective lens (50).

29. The sequencing instrument optical system according to claim 28, wherein, The focal length f1 of the first aspherical lens (31) is greater than 5 mm.

30. The sequencing instrument optical system according to claim 24, characterized in that, The sequencing instrument optical system further includes a beam splitting element, the beam splitting element is located between at least two lenses with the same focal length, and the beam splitting element is used to separate the light of different wavelengths emitted by the light source in the first direction.

31. A sequencing method, characterized in that, Including: Outputting a rectangular spot through a laser; Compressing the rectangular spot in the short axis direction of the rectangular spot through the first shaping module, the first shaping module includes a plurality of lenses, at least two of the plurality of lenses have the same focal length, and at least two lenses with the same focal length are located between the laser and the field stop (40); Expanding the rectangular spot in the long axis direction of the rectangular spot through the second shaping module, the second shaping module includes a plurality of lenses, and the focal lengths of the plurality of lenses are different; Using a beam splitting element to separate the rectangular spot in the short axis direction; Transmit the shaped and split rectangular light spot through the objective lens (50) to the sample to be detected.

32. The sequencing method according to claim 31, wherein In the step of outputting a rectangular light spot by the laser, it includes: Provide a laser beam to the multimode optical fiber through the laser; Guide the laser beam through the multimode optical fiber, and shape the beam output from the output end of the multimode optical fiber into a rectangular light spot by a collimator.

33. The sequencing method according to claim 31, wherein The step of compressing the rectangular light spot in the short axis direction of the rectangular light spot by the first shaping module and the step of expanding the rectangular light spot in the long axis direction of the rectangular light spot by the second shaping module are carried out synchronously.

34. An optical detection method for biological samples, characterized in that, It includes: Output a rectangular light spot by the laser; Expand the rectangular light spot in the long axis direction of the rectangular light spot through the first shaping module, and the first shaping module includes multiple lenses, at least two of the multiple lenses have the same focal length, and at least two of the lenses with the same focal length are located between the laser and the field stop (40); Compress the rectangular light spot in the short axis direction of the rectangular light spot through the second shaping module, and the second shaping module includes multiple lenses with different focal lengths; Transmit the shaped rectangular light spot through the objective lens (50) to the sample to be detected.

35. The optical detection method for biological samples according to claim 34, characterized in that, The sample to be detected is a tissue sample or a nucleic acid sequencing library.

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